Identification of potential microRNAs and their targets in promoting gefitinib resistance by integrative network analysis

Non-small cell lung cancer (NSCLC) accounts for about 80-85% of lung cancers. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib are considered the best choice for first-line treatment for the patients with NSCLC harboring EGFR-activating alterations. Nonetheless, 10-30% of patients may not obtain an

Collectively, these findings suggest that the upregulation of miR-342-3p contributes to gefitinib resistance by targeting CPA4, which may serve as a potential treatment option to overcome gefitinib resistance in patients with NSCLC.

We reported that over-expression of miR-342-3p could significantly increase the resistance to gefitinib of A549/GR and PC9/GR cells and vice versa. Then, we recognized CPA4 as a target of hsa-miR-342-3p by a luciferase reporter assay. The increase in hsa-miR-342-3p levels led to a significant reduction in CPA4 protein expression. However, the opposite results were observed upon miR-342-3p knockdown. Finally, we found that enforced CPA4 expression partially reversed miR-342-3p effects in A549/GR cells. Conclusions: Collectively, these findings suggest that the upregulation of miR-342-3p contributes to gefitinib resistance by targeting CPA4, which may serve as a potential treatment option to overcome gefitinib resistance in patients with NSCLC.